Left Atrial Mechanical Function and Incident Ischemic Cerebrovascular Events Independent of AF: Insights From the MESA Study

Abstract

Objectives: This study sought to assess the association of baseline left atrial (LA) phasic function measured with cardia magnetic resonance (CMR) and incident ischemic cerebrovascular events (CVE).

Background: LA remodeling is a known predictor of atrial fibrillation (AF), which is a risk factor for ischemic CVE. Despite studies showing an association between LA remodeling and ischemic CVE, the association of LA mechanical function with ischemic CVE in a population free of known cardiovascular disease is not fully studied.

Methods: Phasic LA volumes; total, passive, and active LA emptying fractions (LAEF); and peak longitudinal LA strain were measured using feature-tracking CMR in 4,261 MESA (Multi-Ethnic Study of Atherosclerosis) participants (61 ± 10 years of age; 48% male). All individuals were free of clinical cardiovascular disease at baseline. Participants were followed for 11.6 ± 3.5 years for the diagnosis of incident ischemic CVE, defined as ischemic stroke or transient ischemic attack adjudicated by vascular neurologists.

Results: During the follow-up, 193 (1.26 per 1,000 person-years) ischemic CVE (134 ischemic strokes and 59 TIAs) occurred. Individuals with incident ischemic CVE had larger LA volumes and lower passive, active, and total LAEFs at baseline. In multivariate analysis adjusted for known CVE risk factors, left ventricular mass and interim AF, total LAEF was associated with incident ischemic CVE (hazard ratio [HR]: 0.85 per SD; 95% confidence interval [CI]: 0.74 to 0.98; p = 0.027). The unadjusted HR for the lowest tertile of total LAEF compared to the highest tertile was 2.0 (95% CI: 1.43 to 2.79; p < 0.001), and the adjusted HR was 1.47 (95% CI: 1.04 to 2.05; p = 0.031). Addition of total LAEF to known clinical risk factors of CVE and left ventricular mass resulted in an improved predictive accuracy (C statistic of 0.76 vs. 0.73, respectively; p = 0.039).

Conclusions: Reduced total LAEF was associated with incident ischemic CVE independent of known cerebrovascular risk factors and incident AF. Assessment of LA function may add further information in stratifying asymptomatic individuals at risk for ischemic stroke.

Keywords: atrial fibrillation; atrial function; cardiac magnetic resonance; ischemic stroke; left atrial remodeling.

FIGURE 1. Feature Tracking Derived Left Atrial Volume and Strain Curves

(Left) Changes in LA volume during cardiac cycle (ventricular systole and diastole). Maximum, pre-atrial contraction, and minimum LA volumes (points A, B, and C, respectively) were measured using LA volume curve. (Right) Changes in LA longitudinal strain during cardiac cycle. Point D indicates peak longitudinal strain. LA = left atrium.

FIGURE 2. Atrial Variables by Strata of Atrial Fibrillation and Stroke/TIA

Bars demonstrate the means of each measured atrial variable by strata of atrial fibrillation and ischemic cerebrovascular events. AF = atrial fibrillation; LA = left atrial; TIA = transient ischemic attack.

FIGURE 3. Total Left Atrial Emptying Fraction and Incident Ischemic Cerebrovascular Events

The plot demonstrates the results of a restricted cubic spline model. The pink area above and below the pink line indicates the 95% confidence interval.

FIGURE 4. Kaplan-Meier Event-Free Survival Curves

Kaplan-Meier survival curves showing the event-free survival of participants based on tertiles of total left atrial emptying fraction. The first tertile includes participants with the highest total LAEF, and the third tertile includes participants with the lowest total LAEF. LAEF = left atrial emptying fraction.

FIGURE 5. Kaplan-Meier Event-Free Survival Curves in Individuals With CHA₂DS₂-VASc Score ≤1

Kaplan-Meier survival curves show the event-free survival of participants based on tertiles of total left atrial emptying fraction. The first tertile includes participants with the highest total LAEF, and the third tertile includes participants with the lowest total LAEF. CHA₂DS₂-VASc = congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, Prior stroke, transient ischemic attack [TIA], or thromboembolism, Vascular disease, Age 65–74 years, Sex category [female]); other abbreviations as in Figure 4.

Central Illustration. Factors leading to LA Remolding and Their Relationships to Ischemic Stroke

Shared risk factors results in mechanical, structural, and electrical LA remodeling. Electrical changes promote AF development which also worsens LA remodeling. Mechanical changes increase blood stasis and risk of thromboembolism.